Patricia Woo

Background: Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira^®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective: To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design: This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting: The setting was tertiary care centres throughout the UK. Participants: Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions: All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures: Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results: A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions: Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work: A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified. Trial registration: Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20 mg/0.8 ml and 40 mg/0.8 ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres.

The clinical practice of introducing anti-inflammatory therapies in paediatric autoimmune disorders has changed substantially in the last two decades. This is partly due to the fact that we are able to put disease into remission with potent drugs, and so the issue of when to introduce these drugs is important. This review will seek to highlight the consequences of chronic inflammation and the change to outcomes if adequate or 'aggressive' treatment is given early to induce remission. The review not only highlights publications on this topic over the past 12-18 months but also refers to key publications before when appropriate. The disorders reviewed are juvenile idiopathic arthritis, systemic lupus erythematosis, Wegener's granulomatosis, juvenile dermatomyositis, juvenile scleroderma and autoinflammatory syndromes. Outcomes can be influenced by potent anti-inflammatory therapies. Their use early in the evolution of the disorder in question can limit damage and allow the possibility of normal life and function in the child.

The camptodactyly‐arthropathy‐coxa vara‐pericarditis syndrome (CACP) is an autosomal recessive condition characterized by the association of congenital or early onset camptodactyly and noninflammatory arthropathy with synovial hyperplasia. Progressive coxa vara deformity and/or noninflammatory pericardial or pleural effusions have been observed in some patients. Recently, the disease gene has been assigned to human chromosome region 1q25‐q31, and truncating mutations have been identified in the megakaryocyte stimulating factor gene. Studying 12 patients from 8 unrelated families, we emphasized hip and spine involvement, particularly in the course of the disease as shown in a 58‐year‐old patient. Despite clinical variability, linkage studies support genetic homogeneity of the disease. Am. J. Med. Genet. 95:233–236, 2000.